Abstract

Background

A potential strategy for treatment of sickle cell disease (SCD) and β-thalassemia
in adults is reactivation of the ε- and γ-globin genes in the adult. We aimed to identify
trans-activators of ε- and γ-globin expression and provide new candidate targets for
effective treatment of sickle cell disease (SCD) and β-thalassemia through activation
of ε- and γ-globin genes in adults.

Results

We identified a CTD small phosphatase like 2 (CTDSPL2) gene that had higher transcription
levels in umbilical cord blood (UCB) than in adult bone marrow (BM). Also, transcription
of the CTDSPL2 gene increased significantly during erythroid differentiation. Further,
we found that overexpression of CTDSPL2 could obviously improve the expression of
ε- and γ-globin genes in K562 cells. Meanwhile, the repression of CTDSPL2 by RNA interference
decreased expression of ε- and γ-globin genes but did not inhibit the increase of
globin gene expression during K562 erythroid differentiation. In addition, the enforced
expression of CTDSPL2 gene mediated by lentiviruses could also increase ε- and γ-globin
gene expression during erythroid differentiation of CD34+ cells derived from UCB.

Conclusion

CTDSPL2 gene can obviously improve the expression of ε- and γ-globin genes in K562
cells and CD34+ cells derived from UCB. Our study provides a new candidate target
for effective treatment of SCD and β-thalassemia.